The growth of the hair and its renewal are mainly determined by the activity of the hair follicles and of their matrix environment. Their activity is cyclical and essentially comprises three phases, namely the anagen phase, the catagen phase and the telogen phase.
The anagen phase (active or growth phase), which lasts several years and during which the hair lengthens, is succeeded by a very short and transitory catagen phase, which lasts a few weeks. During this phase, the hair undergoes a change, the follicle atrophies and its implantation in the skin appears less and less deep.
The terminal phase or telogen phase, which lasts several months, corresponds to a resting phase of the follicle and the hair finishes by falling out. At the end of this resting period, a new follicle is regenerated there and another cycle recommences.
The hair is therefore continuously renewed and, of the approximately 150 000 individual hairs which make up the hair, approximately 10% are at rest and will be replaced in a few months.
The natural loss of the hair can be estimated, on average, at a few hundred hairs per day for a normal physiological state. This constant physical renewal process undergoes a natural change during the course of ageing; the hairs become finer and their cycles shorter.
In addition, various causes can result in a significant, temporary or definitive, hair loss. The hair can be lost or detrimentally affected during recovery from pregnancy (post partum), during conditions of undernourishment or of dietary imbalances or during conditions of asthenia or of hormonal dysfunctioning, as may be the case during the course of or during recovery from the menopause. Hair can also be lost or detrimentally affected in connection with seasonal phenomena.
It may also be a matter of alopecia, which is essentially due to a disturbance of hair renewal which results, first, in an acceleration in the frequency of the cycles to the detriment of the quality of the hair and then of its amount. The successive growth cycles result in hair which is increasingly fine and increasingly short, which is gradually converted to an unpigmented down and which thus results in a gradual thinning of the head of hair. Areas are preferentially affected, in particular the temples or the front of the head in men, and, in women, a diffuse alopecia of the vertex is observed.
The term “alopecia” also covers a whole family of conditions of the hair follicle having, as a final consequence, partial or general permanent hair loss. It is a matter more particularly of androgenic alopecia. In a significant number of cases, early hair loss takes place in genetically predisposed subjects; it is then a matter of androchronogenetic alopecia. This form of alopecia affects men in particular.
Furthermore, it is known that certain factors, such as hormonal imbalance, physiological stress or malnutrition, can accentuate the phenomenon.
In some dermatosis conditions of the scalp with an inflammatory nature, such as, for example, psoriasis or seborrhoeic dermatitis, hair loss can be greatly increased or can result in highly disrupted cycles of the follicles.
There has been a search for many years, in the cosmetic or pharmaceutical industry, for compositions which make it possible to eliminate or reduce alopecia and in particular to induce or stimulate hair growth or to decrease hair loss.
From this viewpoint, a large number of compositions comprising very diverse active principles, such as, for example, 2,4-diamino-6-piperidinopyrimidine 3-oxide or “minoxidil”, disclosed in U.S. Pat. No. 4,139,619 and U.S. Pat. No. 4,596,812, or its numerous derivatives, such as those disclosed, for example, in Patent Applications EP 0 353 123, EP 0 356 271, EP 0 408 442, EP 0 522 964, EP 0 420 707, EP 0 459 890 and EP 0 519 819, have already been provided.
Clinical studies have demonstrated that PGF2α analogues have the property of bringing about the growth of body hairs and eyelashes in man and animals (Murray A. and Johnstone M. D., 1997, Am. J. Opht., 124(4), 544-547). In man, tests carried out on the scalp have shown that a prostaglandin E2 analogue (viprostol) has the property of increasing hair density (Roenig H H., 1988, Clinic Dermatol., 6(4), 119-121).
Furthermore, Patent WO 98/33497 discloses pharmaceutical compositions comprising prostaglandins or prostaglandin derivatives intended to combat hair loss in man. Prostaglandins of the A2, F2α and E2 type are mentioned as preferred.
However, prostaglandins are molecules with a very short biological half-life which act autocrinally or paracrinally, this reflecting the local and labile nature of the metabolism of prostaglandins (Narumiya S. et al., 1999, Physiol. Rev., 79(4), 1193-1226).
It thus appears important, to maintain and/or increase hair density in man, to retain the endogenous reserves of PGF2α and of PGE2 in the various compartments of the hair follicle or of its immediate cutaneous environment.
A solution which gives good results is the use of compounds which are inhibitors of lipoxygenase and/or inducers of cyclooxygenase for the purpose of promoting hair growth; one hypothesis is that the use of such compounds directs the metabolism of the fatty acids towards the endogenous synthesis of prostaglandins in preference to other routes.
However, to further improve the results, it would be desirable to be able to prolong the activity of the prostaglandins involved in the growth and the preservation of the individual living hair.
Furthermore, it is well known that the programmes of differentiation of the keratinocytes of the epidermis and of the hair follicle are clearly different. Thus, it is known that the keratins of the hair shaft represents a family (Langbein et al., 2001, J. Biol. Chem., 276, 35123-35132) distinct from that expressed in the epidermis, that differentiation markers such as keratins K1 and K10 are not expressed in the hair follicle and in particular in the outer sheath (Lenoir et al., 1988, Dev. Biol., 130, 610-620), that trichohyalin (O'Guin et al., 1992, J. Invest. Dermatol., 98, 24-32) and keratin K6irs (Porter et al., 2001, Br. J. Dermatol., 145, 558-568) are expressed in the hair follicle, in particular in the inner sheath, but not in the epidermis, and that cyclooxygenase type 1, while it is expressed in the epidermis, is not expressed in the keratinocytes of the hair follicle but in the dermal papilla (Michelet et al., 1997, J. Invest. Dermatol., 108, 205-209).
The Applicant has now demonstrated that an enzyme specifically involved in the decomposition of these prostaglandins is present in the dermal papilla of the individual hair, which is a determining compartment for the life of the individual hair. This is because the Applicant has now proved the presence of 15-hydroxyprostaglandin dehydrogenase (abbreviated to 15-PGDH) therein. In addition, it has shown that the inhibition of 15-PGDH has a beneficial effect on hair growth.
This is why the present invention relates to a composition for the care or treatment of human keratinous fibres and in particular hair fibres comprising at least one specific inhibitor of 15-hydroxyprostaglandin dehydrogenase and a physiologically acceptable medium.
15-PGDH is a key enzyme in the deactivation of prostaglandins, in particular of PGF2α and of PGE2, which are important mediators of the growth and survival of the individual hair. It corresponds to the EC 1.1.1.141 classification and is NAD+-dependent. It has been isolated from pig kidney; its inhibition by a thyroid hormone, triiodothyronine, at doses much greater than physiological doses has in particular been observed.
However, provision had never been made to use a 15-PGDH inhibitor for maintaining and/or increasing the density of human keratinous fibres and in particular hair density and/or for reducing the heterogeneity in the diameters of keratinous fibres and in particular of head hairs in man. Increasing the density of keratinous fibres and in particular hair density is understood to mean increasing the number of keratinous fibres and in particular of head hairs per cm2 of skin or scalp.